Lumacaftor

The CFTR protein is a chloride channel present at the surface of epithelial cells in multiple organs. The F508del mutation results in protein misfolding, causing a defect in cellular processing and trafficking that targets the protein for degradation and therefore reduces the quantity of CFTR at the cell surface.

• ORKAMBI is indicated for the treatment of cystic fibrosis (CF) in patients aged 1 year and older who are homozygous for the F508del mutation in the CFTR gene. If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene.

• None. None.contraindicated

Age Group Weight Dose Administration 1 through 2 years 7 kg to <9 kg 1 packet of lumacaftor 75 mg/ivacaftor 94 mg granules Mixed with one teaspoon (5 mL) of soft food or liquid and administered orally every 12 hours with fat-containing food 9 kg to <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg granules 2 through 5 years <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg granules 6 through 11 years - 2 tablets of lumacaftor 100 mg/ivacaftor 125 mg (lumacaftor 200 mg/ivacaftor 250 mg per dose) Taken orally every 12 hours with fat-containing food 12 years and older - 2 tablets of lumacaftor 200 mg/ivacaftor 125 mg (lumacaftor 400 mg/ivacaftor 250 mg per dose) Reduce dosage in patients with moderate or severe hepatic impairment. ( 2.2 , 8.6 , 12.3 ) When initiating ORKAMBI in patients taking strong CYP3A inhibitors, reduce ORKAMBI dosage for the first week of treatment. ( 2.3 , 7.1 , 12.3 ) 2.1 Recommended Dosage in Adults and Pediatric Patients Aged 1 Year and Older The recommended dosage of ORKAMBI in adults and pediatric patients aged one year and older is based on patient's age and weight as described in Table 1.

Use in patients with advanced liver disease: ORKAMBI should be used with caution in these patients and only if the benefits are expected to outweigh the risks. If ORKAMBI is used in these patients, they should be closely monitored after the initiation of treatment and the dosage should be reduced. Liver function decompensation, including liver failure leading to death, has been reported in CF patients with pre-existing cirrhosis with portal hypertension. ( 2.2 , 5.1 , 6.1 ) Liver-related events: Elevated transaminases (ALT/AST) have been observed in some cases associated with elevated bilirubin. Measure serum transaminases and bilirubin before initiating ORKAMBI, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of ALT, AST, or bilirubin elevations, more frequent monitoring should be considered. Interrupt dosing in patients with ALT or AST >5 × upper limit of normal (ULN), or ALT or AST >3 × ULN with bilirubin >2 × ULN. Following resolution, consider the benefits and risks of resuming dosing. ( 5.2 , 6.1 ) Hypersensitivity reactions: Angioedema and anaphylaxis have been reported with ORKAMBI in the postmarketing setting. Initiate appropriate therapy in the event of a hypersensitivity reaction. ( 5.3 ) Intracranial hypertension: Intracranial hypertension (IH) has been reported in the postmarketing setting with the use of ORKAMBI. If an unusual headache or visual disturbances occur during treatment, and IH is suspected, interrupt ORKAMBI and refer for prompt medical evaluation.

The following adverse reactions are discussed in greater detail in other sections of the label: Use in Patients with Advanced Liver Disease [see Warnings and Precautions (5.1) ] Liver-related Events [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions, Including Anaphylaxis [see Warnings and Precautions (5.3) ] Intracranial Hypertension [see Warnings and Precautions (5.4) ] Neuropsychiatric Events, Including Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.5) ] Respiratory Events [see Warnings and Precautions (5.6) ] Effect on Blood Pressure [see Warnings and Precautions (5.7) ] Cataracts [see Warnings and Precautions (5.9) ] The most common adverse reactions to ORKAMBI (occurring in ≥5% of patients with CF homozygous for the F508del mutation in the CFTR gene) were dyspnea, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, fatigue, respiration abnormal, blood creatine phosphokinase increased, rash, flatulence, rhinorrhea, influenza. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Vertex Pharmaceuticals Incorporated at 1-877-634-8789 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

8.1 Pregnancy Risk Summary There are limited and incomplete human data from clinical trials and postmarketing reports on use of ORKAMBI or its individual components, lumacaftor or ivacaftor, in pregnant women to inform a drug-associated risk. In animal reproduction studies, oral administration of lumacaftor to pregnant rats and rabbits during organogenesis demonstrated no adverse effects on fetal development at doses that produced maternal exposures up to approximately 8 (rats) and 5 (rabbits) times the exposure at the maximum recommended human dose (MRHD). Oral administration of ivacaftor to pregnant rats and rabbits during organogenesis demonstrated no adverse effects on fetal development at doses that produced maternal exposures up to approximately 7 (rats) and 45 (rabbits) times the exposure at the MRHD. No adverse developmental effects were observed after oral administration of either lumacaftor or ivacaftor to pregnant rats from organogenesis through lactation at doses that produced maternal exposures approximately 8 and 5 times the exposures at the MRHD, respectively (see Data ) . There are no animal reproduction studies with concomitant administration of lumacaftor and ivacaftor. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S.

Metabolism

The exposure (AUC) of lumacaftor is approximately 2-fold higher in healthy adult volunteers compared to exposure in patients with CF. The exposure of ivacaftor is similar between healthy adult volunteers and patients with CF.

There have been no reports of overdose with ORKAMBI. The highest repeated dose was lumacaftor 1000 mg once daily/ivacaftor 450 mg q12h administered to 49 healthy subjects for 7 days in a trial evaluating the effect of ORKAMBI on electrocardiograms (ECGs). Adverse events reported at an increased incidence of ≥5% compared to the lumacaftor 600 mg/ivacaftor 250 mg dosing period and placebo included: headache (29%), transaminase increased (18%), and generalized rash (10%). No specific antidote is available for overdose with ORKAMBI. Treatment of overdose consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.

• Jul 2, 2015NDANDA206038Vertex Pharms Inc
• Aug 7, 2018NDANDA211358Vertex Pharms Inc

1. 1Infective Pulmonary Exacerbation Of Cystic Fibrosis1,46117%
2. 2Hospitalisation88710%
3. 3Dyspnoea5556.5%
4. 4Pulmonary Function Test Decreased3974.7%
5. 5Cough3944.6%
6. 6Infection3694.3%
7. 7Chest Discomfort3434.0%
8. 8Cystic Fibrosis3263.8%
9. 9Pneumonia2693.2%
10. 10Malaise2242.6%
11. 11Nasopharyngitis2022.4%
12. 12Fatigue1992.3%
13. 13Diarrhoea1932.3%
14. 14Respiration Abnormal1912.2%
15. 15Influenza1842.2%

The 10 most recently updated of 48 ClinicalTrials.gov registrations naming Lumacaftor as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Validation of Respiratory Epithelial Functional Assessment to Predict Clinical Efficacy of Orkambi®.
  Completed · Interventional · 91 enrolled · Assistance Publique - Hôpitaux de Paris
  NCT03894657updated 2026-03-10
• Modulate-CF: Cystic Fibrosis Transmembrane Regulator (CFTR) Biomarker Study to Evaluate the Rescue of Mutant CFTR in Patients With Cystic Fibrosis Treated With CFTR-modulators
  Recruiting · Observational · 500 enrolled · Charite University, Berlin, Germany
  NCT04732910updated 2026-02-24
• Personalized Theratyping Trial
  Recruiting · Early phase 1 · Interventional · 20 enrolled · George Solomon
  NCT03587961updated 2026-02-02
• Real-life Follow-up of Cystic Fibrosis Patients Treated With Ivacaftor+Lumacaftor (Orkambi*)
  Completed · Observational · 852 enrolled · Assistance Publique - Hôpitaux de Paris
  NCT03475381updated 2025-12-01
• Cystic Fibrosis Blood Neutrophils
  Completed · Interventional · 47 enrolled · Assistance Publique - Hôpitaux de Paris
  NCT04970225updated 2025-09-12
• Mutation-specific Therapy for the Long QT Syndrome
  Completed · Phase 2 · Interventional · 16 enrolled · Istituto Auxologico Italiano
  NCT04581408updated 2025-04-25
• Long-term Safety of Lumacaftor/Ivacaftor in Participants With Cystic Fibrosis Who Are Homozygous for F508del and 12 to <24 Months of Age at Treatment Initiation
  Completed · Phase 3 · Interventional · 52 enrolled · Vertex Pharmaceuticals Incorporated
  NCT04235140updated 2024-09-19
• Surrogate Markers of Response to New Therapies in Cystic Fibrosis Patients
  Recruiting · Interventional · 75 enrolled · Hôpital Necker-Enfants Malades
  NCT02965326updated 2024-03-12
• : TRANSITION: An Observational Study of Transition From Lumacaftor/Ivacaftor to Tezacaftor/Ivacaftor (Tez/Iva)
  Completed · Observational · 5 enrolled · National Jewish Health
  NCT03445793updated 2024-01-23
• Bioequivalence and Food Effect Bioavailability Study of Lumacaftor Film-Coated Tablets
  Completed · Phase 1 · Interventional · 39 enrolled · Qanatpharma Canada LTD
  NCT05968612updated 2023-12-26

Frequently asked questions

How does Lumacaftor work?

The CFTR protein is a chloride channel present at the surface of epithelial cells in multiple organs. The F508del mutation results in protein misfolding, causing a defect in cellular processing and trafficking that targets the protein for degradation and therefore reduces the quantity of CFTR at the cell surface.

What is Lumacaftor used for?

According to FDA labeling, Lumacaftor carries indications including: ORKAMBI is indicated for the treatment of cystic fibrosis (CF) in patients aged 1 year and older who are homozygous for the F508del mutation in the CFTR gene. If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Lumacaftor?

Lumacaftor is classified as Chloride Channel Activation Potentiators, Cytochrome P450 2B6 Inducers, Cytochrome P450 2C19 Inducers, Cytochrome P450 2C8 Inducers, Cytochrome P450 2C8 Inhibitors, Cytochrome P450 2C9 Inducers, Cytochrome P450 2C9 Inhibitors, Cytochrome P450 3A Inducers, P-Glycoprotein Inducers, P-Glycoprotein Inhibitors.

What are the brand names for Lumacaftor?

Lumacaftor is marketed under brand names including ORKAMBI.

What are the contraindications for Lumacaftor?

Lumacaftor labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.